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DOCK6 Gene Dedicator of Cytokinesis 6

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DOCK6 Gene Dedicator of Cytokinesis 6 DOCK6 gene dedicator of cytokinesis 6 Normal Function The DOCK6 gene provides instructions for making a protein known as a guanine nucleotide exchange factor (GEF). GEFs turn on (activate) proteins called GTPases, which play an important role in chemical signaling within cells. Often referred to as molecular switches, GTPases can be turned on and off. GTPases are turned off ( inactivated) when they are attached (bound) to a molecule called GDP and are activated when they are bound to another molecule called GTP. The DOCK6 protein activates GTPases known as Cdc42 and Rac1 by exchanging GTP for the attached GDP. Once Cdc42 and Rac1 are active, they transmit signals that are critical for various aspects of embryonic development. The DOCK6 protein appears to regulate these GTPases specifically during development of the limbs, skull, and heart. DOCK6 also plays a role in the development of fibers (axons) that extend from nerve cells. Health Conditions Related to Genetic Changes Adams-Oliver syndrome Mutations in the DOCK6 gene cause Adams-Oliver syndrome, a condition characterized by areas of missing skin (aplasia cutis congenita), usually on the scalp, and malformations of the hands and feet. Neurological abnormalities, such as brain or eye malformations and intellectual disability, are more common in DOCK6-related Adams- Oliver syndrome than in cases associated with other genes. Most DOCK6 gene mutations involved in this condition lead to production of an abnormally short DOCK6 protein that is likely unable to function. Other mutations change single protein building blocks (amino acids) in the DOCK6 protein, which impairs the protein's normal function. The inability of DOCK6 to turn on Cdc42 or Rac1 leads to a reduction in their signaling, which impairs proper development of certain tissues, including the skin on the top of the head and the bones in the hands and feet. Other Names for This Gene • AOS2 • dedicator of cytokinesis protein 6 • DOCK6_HUMAN Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 • KIAA1395 • ZIR1 Additional Information & Resources Tests Listed in the Genetic Testing Registry • Tests of DOCK6 (https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=57572[geneid]) Scientific Articles on PubMed • PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28DOCK6%5BTIAB%5D%29+ OR+%28%28AOS2%5BTIAB%5D%29+OR+%28ZIR1%5BTIAB%5D%29%29+AND +%28%28Genes%5BMH%5D%29+OR+%28Genetic+Phenomena%5BMH%5D%29 %29+AND+english%5Bla%5D+AND+human%5Bmh%5D) Catalog of Genes and Diseases from OMIM • DEDICATOR OF CYTOKINESIS 6 (https://omim.org/entry/614194) Research Resources • ClinVar (https://www.ncbi.nlm.nih.gov/clinvar?term=DOCK6[gene]) • NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/57572) References • Miyamoto Y, Torii T, Yamamori N, Ogata T, Tanoue A, Yamauchi J. Akt and PP2Areciprocally regulate the guanine nucleotide exchange factor Dock6 to controlaxon growth of sensory neurons. Sci Signal. 2013 Mar 5;6(265):ra15. doi:10. 1126/scisignal.2003661. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/2346 2102) • Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A. Dock6, a Dock-C subfamily guaninenucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulatesneurite outgrowth. Exp Cell Res. 2007 Feb 15;313(4):791-804. Epub 2006 Dec 6. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/17196961) • Raftopoulou M, Hall A. Cell migration: Rho GTPases lead the way. Dev Biol.2004 Jan 1;265(1):23-32. Review. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/1 4697350) • Shaheen R, Faqeih E, Sunker A, Morsy H, Al-Sheddi T, Shamseldin HE, Adly N, Hashem M, Alkuraya FS. Recessive mutations in DOCK6, encoding the guanidinenucleotide exchange factor DOCK6, lead to abnormal actin Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 2 cytoskeletonorganization and Adams-Oliver syndrome. Am J Hum Genet. 2011 Aug 12;89(2):328-33. doi: 10.1016/j.ajhg.2011.07.009. Epub 2011 Aug 4. Citation on PubMed (https://pub med.ncbi.nlm.nih.gov/21820096) or Free article on PubMed Central (https://www.nc bi.nlm.nih.gov/pmc/articles/PMC3155174/) • Sukalo M, Tilsen F, Kayserili H, Müller D, Tüysüz B, Ruddy DM, Wakeling E, Ørstavik KH, Snape KM, Trembath R, De Smedt M, van der Aa N, Skalej M, Mundlos S,Wuyts W, Southgate L, Zenker M. DOCK6 mutations are responsible for a distinctautosomal-recessive variant of Adams-Oliver syndrome associated with brain andeye anomalies. Hum Mutat. 2015 Jun;36(6):593-8. doi: 10.1002/humu. 22795. Epub2015 Apr 21. Erratum in: Hum Mutat. 2015 Nov;36(11):1112. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/25824905) Genomic Location The DOCK6 gene is found on chromosome 19 (https://medlineplus.gov/genetics/chrom osome/19/). Page last updated on 18 August 2020 Page last reviewed: 1 November 2015 Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 3.
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